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Glutathione (GSH) Synthesis and Metabolism

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Neural Metabolism In Vivo

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 4))

Abstract

The tripeptide glutathione (GSH) is present in brain cells in millimolar concentrations. GSH has many important cellular and extracellular functions, of which the detoxification of reactive oxygen species and of xenobiotics are especially important. In the brain, astrocytes play a central role in the GSH metabolism. Due to their broad metabolic potential astrocytes can utilize various extracellular precursors to produce the amino acids glutamate, cysteine and glycine that are required as cellular substrates for GSH synthesis. In contrast, neurons rely for their GSH synthesis on the availability of extracellular cysteine that is provided by astrocytes. The mechanism involved in this metabolic supply of cysteine includes export of GSH from astrocytes, extracellular processing of the exported GSH by ectoenzymes, and uptake into neurons of the amino acid precursors for GSH synthesis. Disturbances of this metabolic interaction between astrocytes and neurons will affect GSH homeostasis in brain and could contribute to a compromised antioxidative defense in neurological diseases. In this article we will review the current knowledge on the metabolism of GSH in brain cells with a special focus on the mechanisms that are involved in the metabolic supply of cysteine by astrocytes for the synthesis of GSH in neurons.

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Authors and Affiliations

  1. Center for Biomolecular Interactions, Center for Environmental Research and Sustainable Technologies, University of Bremen, 330440, D-28334, Bremen, Germany

    Maike M. Schmidt Ph.D.

  2. Center for Biomolecular Interactions Bremen, University of Bremen, 330440, D-28334, Bremen, Germany

    Ralf Dringen Ph.D.

  3. Center for Environmental Research and Sustainable Technologies, Leobener Strasse, Bremen, Germany

    Ralf Dringen Ph.D.

  4. School of Psychology and Psychiatry, Monash University, Clayton, VIC, Australia

    Ralf Dringen Ph.D.

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  1. Maike M. Schmidt Ph.D.
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Correspondence to Ralf Dringen Ph.D. .

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  1. School of Medicine, Hoglund Brain Imaging Center, University of Kansas, Rainbow Blvd. 3901, Kansas City, 66160, Kansas, USA

    In-Young Choi

  2. Inst. Physique de la Matière Complexe, Labo. d'Imagerie Fonctionnelle et, Ecole Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland

    Rolf Gruetter

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Schmidt, M.M., Dringen, R. (2012). Glutathione (GSH) Synthesis and Metabolism. In: Choi, IY., Gruetter, R. (eds) Neural Metabolism In Vivo. Advances in Neurobiology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1788-0_36

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